title: Bone-marrow mesenchymal stem cells reduce rat intestinal ischemia-reperfusion injury, ZO-1 downregulation and tight junction disruption via a TNF-α-regulated mechanism.
abstract: OBJECTIVE
  To investigate the effect of bone-marrow mesenchymal stem cells (BM MSCs) on the intestinal mucosa barrier in ischemia/reperfusion (I/R) injury.
  
  
  METHODS
  BM MSCs were isolated from male Sprague-Dawley rats by density gradient centrifugation, cultured, and analyzed by flow cytometry. I/R injury was induced by occlusion of the superior mesenteric artery for 30 min. Rats were treated with saline, BM MSCs (via intramucosal injection) or tumor necrosis factor (TNF)-α blocking antibodies (via the tail vein). I/R injury was assessed using transmission electron microscopy, hematoxylin and eosin (HE) staining, immunohistochemistry, western blotting and enzyme linked immunosorbent assay.
  
  
  RESULTS
  Intestinal permeability increased, tight junctions (TJs) were disrupted, and zona occludens 1 (ZO-1) was downregulated after I/R injury. BM MSCs reduced intestinal mucosal barrier destruction, ZO-1 downregulation, and TJ disruption. The morphological abnormalities after intestinal I/R injury positively correlated with serum TNF-α levels. Administration of anti-TNF-α IgG or anti-TNF-α receptor 1 antibodies attenuated the intestinal ultrastructural changes, ZO-1 downregulation, and TJ disruption.
  
  
  CONCLUSIONS
  Altered serum TNF-α levels play an important role in the ability of BM MSCs to protect against intestinal I/R injury.
authors.affiliation: Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin 300192, China.
authors.forename: Zhong-Yang
authors.initials: ZY
authors.lastname: Shen
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Hong-Li
authors.initials: HL
authors.lastname: Song
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zheng
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D016026:Bone Marrow Transplantation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply* / Q000276:immunology / Q000648:ultrastructure; D019344:Lactic Acid / Q000097:blood; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D008641:Mesenteric Vascular Occlusion / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D009092:Mucous Membrane / Q000098:blood supply* / Q000276:immunology / Q000378:metabolism / Q000648:ultrastructure; D010539:Permeability; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000097:blood / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction; D019108:Tight Junctions / Q000378:metabolism*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism*
chemical_list: D015415:Biomarkers; C569044:Tjp1 protein, rat; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; D019344:Lactic Acid; D006631:Amine Oxidase (Copper-Containing)
keywords: Bone marrow mesenchymal stem cells; Intestinal mucosa; Ischemia-reperfusion injury; Tumor necrosis factor-α; Zona occludens 1